Effect of Heterozygosity Loss in HLA Region before Transplantation on HLA Typing in Patients with Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of loss of heterozygosity(LOH) in HLA region at initial diagnosis and remission of leukemia patient before transplantation on HLA typing.</p><p><b>METHODS</b>The HLA typing was performed in DNA extracted from peripheral blood obtained at diagnosis (Sample 1 and Sample 2) and remission (Sample 3) in one pretransplant male patient with mixedphenotype acute leukemia (MPAL). HLA typing for HLA-A, B, C, DQB1, DRB1 was performed by Sequence-based typing (SBT), Sequence-specific oligonucleotide probe hybridization (SSO) and Sequence-specific primers (SSP). To define more precisely a cutoff limit for the detection of a heterozygous DNA present in a fraction of the cells by the SBT technology, DNA mixing experiments were performed.</p><p><b>RESULTS</b>SBT results showed that Sample 1 and Sample 2 were both homozygous HLA results at five loci (lost one haplotype) although the sequencing background of Sample 1 was a little high. Except HLA-C locus was homozygous, Sample 3 was heterozygous HLA results at four loci. Based on DNA mixing experiments, a cutoff limit for the detection of heterozygous DNA was 20% by SBT technology, and a detection threshold for HLA-A, B, C, DQB1, DRB1 heterozygosity in blood samples was <75% blasts.</p><p><b>CONCLUSION</b>Because LOH may be partial, any homozygous HLA result obtained during a blast crisis, especially ≥75% blasts, would have to be confirmed by a second typing on a buccal swab or on peripheral blood from the patient in complete remission.</p>

Clinical survey of cancer-related fatigue in patients with advanced non-small cell lung cancer / 肿瘤

Objective: To examine the incidence of cancer-related fatigue in patients with advanced nonsmallcell lung cancer (NSCLC) and explore the relationship between chemotherapy and cancer-relatedfatigue. Methods: One hundred and twenty patients with advanced NSCLC were enrolled between January2009 and December 2009. All patients received four cycles of platinum-based doublet chemotherapy, andthen they were followed-up for one year. The fatigue score was evaluated before chemotherapy, every 2cycles during the period of chemotherapy and every three months during the follow-up by using fatiguenumerical rating scale. Results: In 120 patients with advanced NSCLC, 29 (24.2%) patients had mild fatigue,64 (53.3%) patients had moderate fatigue, and 27 (22.5%) patients had severe fatigue. The average cancer-relatedfatigue score was increased progressively during chemotherapy and reached the highest value of 5.31after 4 cycles of chemotherapy, and then it tended to decline and touch the lowest value of 3.95 after six-monthfollow-up. The Eastern Cooperative Oncology Group performance status (ECOG PS) score is the onlyone factor related to cancer-related fatigue (P<0.01), and the age, gender, pathology and clinical stagewere not associated with cancer-related fatigue. The fatigue score was decreased in patients with stabledisease (4.26±2.27 vs 3.64±1.75, P<0.01) or partial response (4.27±2.28 vs 2.33plusmn;1.50, P<0.01) after three-month follow-up as compared with that before chemotherapy, whereas the fatigue score was increased in patients with progressive disease (4.48±2.09 vs 5.00±1.75, P<0.01). Conclusion: The cancer-related fatigue occurred in advanced NSCLC with a very high incidence, and the chemotherapy can strengthen the intensity of cancer-related fatigue, which is related to ECOG PS score and response to chemotherapy. Copyright© 2011 by TUMOR.

Polymorphism of adinoponectin gene in pedigree of type 2 diabetes mellitus / 第二军医大学学报

Objective: To investigate the correlation between the single nucleotide polymorphism (SNP) of adiponectin (APM1) gene and type 2 diabetes mellitus. Methods: Three common binding sites (-11377C>G, +45T>G, and +276G> T) of SNP on the APM1 gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in 75 pedigrees (337 individuals) of type 2 diabetes mellitus. Genehunt software was used to analyze the transmission-disequilibrium (TDT) and to calculate SNP combining haplotypes. Meanwhile, the physiological and biochemical parameters were also determined in the pedigrees of type 2 diabetes mellitus. Results: We found no preferential transmission in the tested binding sites or any haplotypes of SNP in the APM1 gene in the filial generation of type 2 diabetes mellitus. In type 2 diabetes mellitus group, GG genotype had higher body mass index (BMD (P=O.032) and waist circumference (WC) (P= 0.030) compared to CC genotype in the patients with SNP-11377 binding site; patients with G allele had lower levels of high-density lipoprotein cholesterol (HDL-C) (P = 0.006) and higher levels of fasting plasma insulin (FINS) (P = 0.011) as compared to CC genotype. However, FINS levels (P=O.021) in subjects with CC genotype were significantly lower than those with G allele in healthy control group. For patients with SNP+45 binding site, those with GG genotypes had higher BMI (P= 0.036) and lower levels of FINS (P = 0.014) than those with TT genotypes in both groups. For patients with SNP + 276 binding site, those with GG genotypes had higher BMI(P = 0.043) than those with T allele in the control group. Conclusion: The SNP of the APM1 gene is not associated with the pedigrees of type 2 diabetes mellitus, but APMl gene has influence on the function of insulin B cells and the development of obesity.

Leukemia cell surface expression of E-cadherin and its correlation with membrane localization of beta-catenin / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the expression of cell surface E-cadherin in leukemia cell and the correlation of cell membrane localization of beta-catenin with E-cadherin expression.</p><p><b>METHODS</b>Bone marrow samples from 46 patients with acute leukemia and 17 normal donors were analyzed. Cell surface expression of E-cadherin and membrane localization of beta-catenin were labeled by immunofluorescence and analyzed with a laser scanning confocal fluorescence microscope in 14 specimens.</p><p><b>RESULTS</b>Cell surface E-cadherin expression level was significantly lower in leukemia cells (with the median fluorescent intensity of 16.78) than in normal hematopoietic progenitors (26.03). Correlation analysis showed that cell membrane localization of beta-catenin was correlated with E-cadherin expression (r = 0.74, P = 0.002). After E-cadherin was induced to express in leukemic cell by 5-Aza-CdR, membranous expression of beta-catenin was elevated while the nuclear expression reduced, indicating that E-cadherin-mediated adhesions could recruit beta-catenin to cell membrane.</p><p><b>CONCLUSION</b>The loss of E-cadherin in leukemia cells may result in beta-catenin translocating to the nuclear and transcriptional activation of its target genes.</p>

Study on the relationship between polymorphisms of peroxisome proliferators-activated receptor-gamma coactivator-1alpha gene and type 2 diabetes in Shanghai Hans in China / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To observe the association between single nucleotide polymorphism (SNP) of peroxisome proliferators-activated receptor-gamma coactivator-1alpha (PGC-1alpha ) gene and type 2 diabetes mellitus(T2DM).</p><p><b>METHODS</b>Four common SNPs of PGC-1alpha gene were genotyped with polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and then analyzed with transmission-disequilibrium test (TDT) and sib transmission-disequilibrium test (STDT) in 69 T2DM pedigrees (310 individuals). Furthermore, the authors performed a case-control study to genotype Gly482Ser in 156 patients with T2DM and 111 normal glucose tolerance people without family history.</p><p><b>RESULTS</b>(1)There were no positive results in four variances in TDT-STDT analysis(P> 0.05). (2)The Gly482Ser exhibited a significant difference between the two groups. GA genotype carriers were at increased risk for T2DM (OR=1.85), and there was statistically significant difference in the allele frequency between the case and control groups(P=0.046). (3) The subjects with GG genotype at position Gly482Ser had a higher HDL-C and lower LDL-C and TG levels when compared against those with GA+AA genotype in the control group without family history(P=0.043,lzP=0.046, P=0.037 respectively).</p><p><b>CONCLUSION</b>This study suggested that the PGC-1alpha gene might be implicated in the pathogenesis of T2DM. But the studied SNPs in PGC-1alpha gene may not be major susceptibility ones of T2DM mellitus in Han people of Shanghai.</p>

Efficacy of calf spleen extraction injection combined chemotherapy in the treatment of advanced nonsmall cell lung cancer / 中国癌症杂志

Background and purpose:The occurrence and development of lung cancer are closely correlated with the immune function in the human body.The patients with malignant tumors have shown a disorder of immune function,especially in terms of loss of cellular immune function.The purpose of this study was to investigate the possible auxiliary effect of sipulin in the treatment of advanced non-small-cell lung cancer(NSCLC).methods: Ninety-three patients were randomly divided into two groups:sipulin group:sipulin plus docetaxel+cisplatin;control group:only administered docetaxel+cisplatin.The leukocyte,haemoglobin and platelet,toxicity of digestive tract,body weight,Karnofsky status and efficacy of those patients were evaluated before and after therapy,respectively.Results: Overall response rates were 46.67% and 30.23%(P=0.023)in sipulin group and control group,respectively.The median survival time was 10.1months versus 8.3 months(P=0.035)in sipulin group and control group,respectively.The 1-year survival rate for sipulin group and control group was 52.9% versus 39.4%(P=0.038),respectively.The clinical efficacy and the frequence of leukocyte reduction were better in sipulin group than in control group,the quality of life and clinical symptom of the patients in sipulin group were improved more significantly than those in control group (P